title: Preoperative chemotherapy followed by concurrent chemoradiation therapy based on hyperfractionated accelerated radiotherapy and definitive surgery in locally advanced non-small-cell lung cancer: mature results of a phase II trial.
abstract: OBJECTIVE
  To evaluate the feasibility and efficacy of an intensive multimodality approach with combination chemotherapy, hyperfractionated accelerated chemoradiotherapy, and definitive surgery in prognostically unfavorable subgroups of locally advanced non-small-cell lung cancer stages IIIA and IIIB (LAD-NSCLC).
  
  
  METHODS
  Following staging, including mediastinoscopy, 94 patients with inoperable LAD-NSCLC were treated preoperatively with chemotherapy (three courses of split-dose cisplatin and etoposide [PE]) followed by concurrent chemoradiotherapy (one course of PE combined with 45 Gy hyperfractionated accelerated radiotherapy). After repeat mediastinoscopy, patients underwent surgery 4 weeks postradiation.
  
  
  RESULTS
  Of 94 consecutive patients (52 stage IIIA [> or = two lymph node levels involved] and 42 stage IIIB [no pleural effusion, no supraclavicular nodes]), 62 (66%) completed induction and underwent surgery. Complete resection (R0) was achieved in 50 (53% of all patients) and pathologic complete response (PCR) in 24 (26%). After a median follow-up of 43 months, the median survival time was 20 months for IIIA, 18 months for IIIB, and 42 months for R0 patients. Calculated survival rates at 4 years were 31%, 26%, and 46%. Two patients died of sepsis preoperatively and four died postoperatively of pleural empyema (n = 1), stump insufficiency (n = 2), and cardiac failure (n = 1). Other toxicities were acceptable-mainly hematologic during chemotherapy or chemoradiotherapy and esophagitis during chemoradiotherapy.
  
  
  CONCLUSIONS
  This intensive multimodality treatment is feasible and demonstrates high efficacy in prognostically unfavorable LAD-NSCLC subgroups with high R0 rates and improved long-term survival compared with historical controls
authors.affiliation: Department of Internal Medicine (Cancer Research), West German Cancer Center, University of Essen Medical School, Essen-Heidhausen, Germany. wilfried.eberhardt@uni-essen.de
authors.forename: W
authors.initials: W
authors.lastname: Eberhardt
authors.forename: H
authors.initials: H
authors.lastname: Wilke
authors.forename: G
authors.initials: G
authors.lastname: Stamatis
authors.forename: M
authors.initials: M
authors.lastname: Stuschke
authors.forename: A
authors.initials: A
authors.lastname: Harstrick
authors.forename: H
authors.initials: H
authors.lastname: Menker
authors.forename: B
authors.initials: B
authors.lastname: Krause
authors.forename: M R
authors.initials: MR
authors.lastname: Müeller
authors.forename: M
authors.initials: M
authors.lastname: Stahl
authors.forename: M
authors.initials: M
authors.lastname: Flasshove
authors.forename: V
authors.initials: V
authors.lastname: Budach
authors.forename: D
authors.initials: D
authors.lastname: Greschuchna
authors.forename: N
authors.initials: N
authors.lastname: Konietzko
authors.forename: H
authors.initials: H
authors.lastname: Sack
authors.forename: S
authors.initials: S
authors.lastname: Seeber
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000601:surgery / Q000628:therapy*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000601:surgery / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011879:Radiotherapy Dosage; D015996:Survival Rate
chemical_list: D005047:Etoposide; D002945:Cisplatin